Premium
Single Plasma Concentrations of 1′‐Hydroxymidazolam or the Ratio of 1′‐Hydroxymidazolam: Midazolam Do Not Predict Midazolam Clearance in Healthy Subjects
Author(s) -
Rogers Janyce F.,
Nafziger Anne N.,
Kashuba Angela D. M.,
Streetman Daniel S.,
Rocci Mario L.,
Choo Edna F.,
Wilkinson Grant R.,
Bertino Joseph S.
Publication year - 2002
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/009127002237986
Subject(s) - midazolam , chemistry , pharmacokinetics , anesthesia , plasma concentration , medicine , pharmacology , sedation
The 30‐minute ratio of 1′‐hydroxymidazolam: midazolam plasma concentrations has been used as a measure of midazolam clearance in liver transplant patients. This study determined if a single concentration of 1′‐hydroxymidazolam or the ratio of 1′‐hydroxymidazolam: midazolam could be used to predict midazolam clearance in healthy subjects. Plasma midazolam and 1′‐hydroxymidazolam concentrations from three previous studies were used for analyses. Data obtained predose and at 5,30, 60,120,240, 300, and 360 minutes following intravenous doses of midazolam in 61 adults were divided and used to derive and validate equations to predict midazolam clearance. Equations were derived using linear regression and then validated by comparing predicted to observed clearance. Only one equation was related to midazolam clearance as a function of 1′‐hydroxymidazolam, but it did not predict midazolam clearance (r = 0.29, p = 0.31). Single sampling of 1′‐hydroxymidazolam or 1′‐hydroxymidazolam: midazolam plasma concentrations cannot be used to predict midazolam clearance in healthy adults.